Synthetic Strategies towards the Generation of Penicillin-Containing Hybrids in the Search for Anticancer Activity.

An extended library of hybrids that combined a penicillin derivative with a peptoid moiety was designed and synthetized using either a solid-phase or a mixed solid-phase/solution-phase strategy. The library was further evaluated for antiproliferative activity. While none of the different synthesized compounds showed significant cytotoxicity against a normal cell line, tumor cell results drew several conclusions, when comparing with our reference, the highly active triazolylpeptidyl penicillin derivative, TAF7f. Thus, when the 1,2,3-triazole group was exchanged by its "retro-inverse" analogue, no change was noted in the activity of the hybrids; however, better performance was generally obtained if the triazole is replaced by a glycine moiety. Additionally, the absence of hydrogen bond donor groups decreased the compounds activity, which could explain that, in general, this set of derivatives were less active than their peptide-containing analogues. From this study, is indisputable that, regardless of the type of chain (peptide, peptoid or mixture) attached to penicillin, an isobutyl side chain placed in the position closest to penicillin and a benzyl in the next position are determinant for the activity.

Design, synthesis and cytotoxic evaluation of peptoid analogs of an anticancer active triazolylpeptidyl penicillin.

Aim: Encouraged by the antitumor activity exhibited by triazolylpeptidyl penicillins, we decided to synthesize and evaluate a library of peptoid analogs. Results: The replacement of the dipeptide unit of the reference compound, TAP7f, was investigated. In addition, the effect of the triazole linking group on the biological activity of these new derivatives was evaluated, exchanging it with a glycine spacer. The cytotoxic effect of the library compounds was determined in the B16-F0 cell line and compared with the effects on normal murine mammary gland cells. Conclusion: Among the tested compounds, peptoid 4e exhibited the highest antiproliferative activity.

Domino Self-Sensitized Photooxygenation of Conjugated Dienones for the Synthesis of 1,2,4-Trioxanes.

The photochemical behavior of several dienones was studied under aerobic conditions. 2-Allylidene-1,3-cycloalkanediones prepared via Knoevenagel-type condensation between simple readily available 1,3-dicarbonyl substrates and α,ß-unsaturated aldehydes afforded 1,2,4-trioxane derivatives upon UVA irradiation in the presence of oxygen. This domino self-sensitized photooxygenation cascade of conjugated carbonyl systems proceeds stereoselectively and involves the formation of two new oxa-cycles, three new bonds (two C-O), and three stereocenters.